The overall goals of this project are to define the factors responsible for the changes which occur in antibody-dependent cellular cytotoxicity (ADCC) levels to herpesvirus-induced membrane antigens (MA) with progression of disease in owl monkeys with Herpesvirus saimiri-induced lymphoma and in patients with EBV associated cancers. Sera from owl monkeys with HVS-associated malignant disease developed remarkably high ADCC titers (greater than 60,000) with progression of disease in comparison to chronically infected monkeys. Natural killer (NK) cytotoxicity associated with Fc-receptor positive T-lymphocytes increased in parallel with ADCC titers against a variety of cell lines suggesting that there might be a relationship between NK and ADCC in this system. Attempts to identify a novel antigen in HVS-transformed or infected cells that serves as the target for ADCC have been negative to date. Two cell lines from HVS-induced lymphomas have now been established in tissue culture. Both are Fc-receptor-negative T-cell lines. Neither cell line was sensitive to NK activity mediated by lymphocytes from normal owl monkeys while both were sensitive to NK cytotoxicity mediated by lymphocytes from leukemic animals. Future studies will be directed at determining the role of ADCC and NK in immunosurveillance against HVS-induced malignancies.